Thus, the aim of the present study was to: (1) evaluate the effect of acute and repeated treatment with the P2RX7 antagonist brilliant blue G (BBG) in animals submitted to the LH model; (2) to investigate if the stress and the antidepressant effect would be associated with altered P2RX7 levels in the hippocampus and frontal cortex, brain regions highly implicated in the neurobiology of depression (Liu et al., 2017). Here, P2RX7 is linked to depressive symptom measurement.